Work in this laboratory has suggested that the alternate pathway (C3 shunt) as well as the classical antibody Clq activation of complement is operative in systemic lupus erythematosus and bullous pemphigoid skin diseases. In herpes gestationis complement activation via the alternate pathway occurs without evidence of the participation of antibody or Clq. In addition, herpes gestationis patients possess serum factor(s) capable of activating and depositing C3 on normal skin basement membranes. We propose to isolate and characterize the serum factor(s) involved. Techniques to be employed in isolation include preparative disc electrophoresis, molecular sieve and ion exchange chromatography, density gradient ultracentrifugation and others as required. We have suggestive evidence that the C3 shunt may be operative in patients with dermatitis herpetiformis having IgA specifically deposited on their skin basement membranes. Further studies using immunofluorescent techniques will be performed on skin biopsies from these patients. Various conjugated anti-complement anti-properdin, anti-C3 PA and anti-immunoglobulin antisera will be employed. We will also test our hypothesis that dapsone, an effective therapy of this uncommon disease, may inhibit complement activation via the C3 shunt. A possible role for the polysaccharide containing basement membrane will also be explored. Experiments are proposed to test whether this membrane acts as a "nonspecific" absorbent of complement and/or C3 shunt components or whether it acts as an activator of the shunt similar to zymosan, inulin and other complex polysaccharides.